TY - JOUR TI - Mechanism of chiral proofreading during translation of the genetic code AU - Ahmad, Sadeem AU - Routh, Satya Brata AU - Kamarthapu, Venu AU - Chalissery, Jisha AU - Muthukumar, Sowndarya AU - Hussain, Tanweer AU - Kruparani, Shobha P AU - Deshmukh, Mandar V AU - Sankaranarayanan, Rajan A2 - Kuriyan, John VL - 2 PY - 2013 DA - 2013/12/03 SP - e01519 C1 - eLife 2013;2:e01519 DO - 10.7554/eLife.01519 UR - https://doi.org/10.7554/eLife.01519 AB - The biological macromolecular world is homochiral and effective enforcement and perpetuation of this homochirality is essential for cell survival. In this study, we present the mechanistic basis of a configuration-specific enzyme that selectively removes D-amino acids erroneously coupled to tRNAs. The crystal structure of dimeric D-aminoacyl-tRNA deacylase (DTD) from Plasmodium falciparum in complex with a substrate-mimicking analog shows how it uses an invariant ‘cross-subunit’ Gly-cisPro dipeptide to capture the chiral centre of incoming D-aminoacyl-tRNA. While no protein residues are directly involved in catalysis, the unique side chain-independent mode of substrate recognition provides a clear explanation for DTD’s ability to act on multiple D-amino acids. The strict chiral specificity elegantly explains how the enriched cellular pool of L-aminoacyl-tRNAs escapes this proofreading step. The study thus provides insights into a fundamental enantioselection process and elucidates a chiral enforcement mechanism with a crucial role in preventing D-amino acid infiltration during the evolution of translational apparatus. KW - homochirality KW - proofreading KW - enzyme mechanism KW - translation JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -